Anandamide induces cough in conscious guinea-pigs through VR1 receptors
Anandamide induces cough in conscious guinea-pigs through VR1 receptors
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DOI：
10.1038/sj.bjp.0704950
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发表时间：
2002-11-01
影响因子：
7.3
通讯作者：
Hey, JA
中科院分区：
文献类型：
--
作者：
Jia, YL;McLeod, RL;Hey, JA
1内源性神经细胞脂质介质Anandamide是大麻素(CB)和香草素受体(VR)的配体，可在肺内合成。阿南达胺的致咳作用尚未被研究过。本研究旨在探讨氨苯乙胺对清醒豚鼠的直接致咳作用及其对原代豚鼠结状神经节神经元VR1受体功能的影响。2安非他胺(0.3-3 mg·ml(-1))雾化吸入后，以浓度依赖的方式引起清醒豚鼠咳嗽。VR1拮抗剂卡萨西平对豚鼠的咳嗽有明显的抑制作用。预先给予CBI(SR 141716A)和CB2(SR 144528)拮抗剂对阿南达胺诱发的咳嗽无影响。这些结果表明，ANANDAME诱导的咳嗽是通过激活VR1受体来实现的。3 ANANDAME(10-100微米)增加了豚鼠结状神经节细胞内钙离子浓度，通过Fluo-4荧光变化来估计。两种不同的VR1拮抗剂卡萨西平(Capsazepine，1um)和I-RTX(Idoresiniferatoxin，0.1um)均能抑制Anandamide诱导的钙反应，表明Anandamide诱导的钙反应是通过激活VR1通道实现的。相反，CB1(SR 141716A，1um)和CB2(SR 144528，0.1um)受体拮抗剂对Anandamide的钙反应没有影响。4综上所述，这些结果提供了Anandamine激活豚鼠结状神经节细胞天然香草素受体并通过激活vr1受体而引起咳嗽的证据。
1 Endogenous neuronal lipid mediator anandamide, which can be synthesized in the lung, is a ligand of both cannabinoid (CB) and vanilloid receptors (VR). The tussigenic effect of anandamide has not been studied. The current study was designed to test the direct tussigenic effect of anandamide in conscious guinea-pigs, and its effect on VR1 receptor function in isolated primary guinea-pig nodose ganglia neurons.2 Anandamide (0.3-3 mg-ml(-1)), when given by aerosol, induced cough in conscious guinea-pigs in a concentration dependent manner. When guinea-pigs were pretreated with capsazepine, a VR1 antagonist, the anandamide-induced cough was significantly inhibited. Pretreatment with CBI (SR 141716A) and CB2 (SR 144528) antagonists had no effect on anandamide-induced cough. These results indicate that anandamide-induced cough is mediated through the activation of VR1 receptors.3 Anandamide (10-100 muM) increased intracellular Ca2+ concentration estimated by Fluo-4 fluorescence change in isolated guinea-pig nodose ganglia cells. The anandamide-induced Ca2+ response was inhibited by two different VR1 antagonists: capsazepine (1 muM) and iodoresiniferatoxin (I-RTX, 0.1 muM), indicating that anandamide-induced Ca2+ response was through VR1 channel activation. In contrast, the CB1 (SR 141716A, 1 muM) and CB2 (SR 144528, 0.1 muM) receptor antagonists had no effect on Ca2+ response to anandamide.4 In conclusion, these results provide evidence that anandamide activates native vanilloid receptors in isolated guinea-pig nodose ganglia cells and induces cough through activation of VR1 receptors.